Sleep’s role in the reprocessing and restructuring of memory Anne Catharina Maria Koopman A thesis submitted for the degree of Doctor of Philosophy Cardiff University School of Psychology July 2020 Thesis Summary Sleep disconnects us from our external environment and puts us in a vulnerable state, yet it is surprisingly universal. This thesis looks at the cognitive functions of sleep; specifically, the role of sleep in reprocessing and restructuring memory. It is now well-known that sleep actively consolidates memories, and even restructures them. This is likely achieved through the reactivation of memory representations. Previous research has shown that such reactivations can be triggered with a method called targeted memory reactivation (TMR). In Chapter 2, I used TMR during rapid eye movement (REM) and slow-wave sleep (SWS) to investigate the effect of cueing in these stages on electrophysiology and subsequent task behaviour in a two-handed serial reaction time task. TMR during SWS led to detectable memory reactivation, and significant behavioural improvements in the non-dominant but not the dominant hand. TMR during REM did not affect behaviour, although electrophysiological results indicated that cues were processed during this stage. Chapter 3 examined the effects of REM and SWS TMR on an associative memory task. We did not find any effect of SWS TMR. On the other hand, REM TMR improved remote associations between items which were not learned together but whose relationship could be inferred, indicating a role for REM sleep in memory restructuring. This was supported by a difference in event-related potentials in response to memory-related and control cues. However, two replications of the REM group showed that these results were not reliable. Chapter 4, finally, looked at the effects of wakefulness and sleep on two creative tasks. The more word-based task indeed benefitted from an interval containing sleep, but the more conceptual task showed improvements relating to wakefulness and time of day. Together, these results increase our understanding of how different sleep stages, wakefulness, and memory reactivation all influence the restructuring of memory. v vi Declaration and Statements DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is it being submitted concurrently for any other degree or award (outside of any formal collaboration agreement between the University and a partner organisation). Signed: Anne Koopman____ Date: 09/07/2020 STATEMENT 1 This thesis is being submitted in partial fulfilment of the requirements for the degree of PhD. Signed: Anne Koopman____ Date: 09/07/2020 STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the views expressed are my own. Other sources are acknowledged by explicit references. The thesis has not been edited by a third party beyond what is permitted by Cardiff University's Use of Third Party Editors by Research Degree Students Procedure. Signed: Anne Koopman____ Date: 09/07/2020 STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available in the University’s Open Access repository (or, where approved, to be available in the University’s library and for inter-library loan), and for the title and summary to be made available to outside organisations, subject to the expiry of a University-approved bar on access if applicable. Signed: Anne Koopman____ Date: 09/07/2020 WORD COUNT: 59,311 (Excluding summary, acknowledgements, declarations, contents pages, appendices, tables, diagrams and figures, references, bibliography, footnotes and endnotes) vii viii Table of Contents Thesis Summary .................................................................................................................................. v Declaration and Statements ............................................................................................................. vii Acknowledgements .......................................................................................................................... xiii Contributors ...................................................................................................................................... xv CHAPTER 1: General introduction .................................................................................................... 17 1.1 Preface .................................................................................................................................... 18 1.2 Sleep physiology...................................................................................................................... 19 1.3 Sleep and Memory .................................................................................................................. 21 1.3.1 Memory processes and systems ...................................................................................... 22 1.3.2 Models of sleep & memory .............................................................................................. 23 1.4 Memory reactivation and Targeted Memory Reactivation (TMR) ......................................... 26 1.4.1 Spontaneous reactivation ................................................................................................ 26 1.4.2 Targeted Memory Reactivation (TMR) ............................................................................ 29 1.4.3 Detection of human (sleep) reactivations ....................................................................... 31 1.5 The restructuring of memories during sleep .......................................................................... 34 1.5.1 Regularity abstraction and generalisation ....................................................................... 34 1.5.2 Associative inference ....................................................................................................... 36 1.5.3 Creativity .......................................................................................................................... 37 1.6 Summary ................................................................................................................................. 41 1.7 Research objectives ................................................................................................................ 42 CHAPTER 2: Targeted memory reactivation of a serial reaction time task in SWS, but not REM, preferentially benefits the non-dominant hand ............................................................................ 45 2.1 Abstract ................................................................................................................................... 46 2.2 Introduction ............................................................................................................................ 46 2.3 Materials and Methods ........................................................................................................... 49 2.3.1 Participants ...................................................................................................................... 49 2.3.2 Experimental tasks and design......................................................................................... 49 2.3.3 PSG data acquisition and analysis .................................................................................... 53 2.3.4 Electrophysiological analysis ............................................................................................ 54 2.3.5 Spindle analysis ................................................................................................................ 55 2.3.6 Behavioural analysis ......................................................................................................... 56 2.3.7 Classification .................................................................................................................... 58 2.4 Results ..................................................................................................................................... 60 2.4.1 Sleep parameters ............................................................................................................. 60 ix 2.4.2 Behaviour: Both Hands .................................................................................................... 61 2.4.3 Behaviour: Left and Right Hand ....................................................................................... 62 2.4.4 Electrophysiology: Spindle analysis ................................................................................. 63 2.4.5 Electrophysiology: Event-related potentials ................................................................... 65 2.4.6 Classification .................................................................................................................... 66 2.4.7 Correlating classification performance with behaviour .................................................. 69 2.5 Discussion ............................................................................................................................... 70 2.5.1 TMR in SWS but not REM benefits SRTT consolidation ................................................... 71 2.5.2 TMR preferentially benefits the non-dominant hand ..................................................... 72 2.5.3 Linear classifier with time domain features detects reactivation in SWS ....................... 73 2.5.4 Conclusion ......................................................................................................................